The epilepsies constitute one of the most common neurological disorders affecting 40 million people worldwide (1). Within the spectrum of epileptic syndromes is a group of heterogeneous inherited disorders named the Progressive Myoclonus Epilepsies (PME) in which progressive neurological decline and worsening primarily myoclonic seizures follow an initial period of normal development (2, 3, 4). Lafora's disease (LD) is an autosomal recessive and genetically heterogeneous form of Progressive Myoclonus Epilepsy characterized by polyglucosan inclusions seizures and cumulative neurological deterioration. The onset occurs during late childhood and usually results in death within a decade of first symptoms. With few exceptions, patients with LD follow a homogeneous clinical course (4) despite the existence of genetic locus heterogeneity (5). Biopsy (or autopsy) of various tissues including brain, liver, muscle, and skin reveals characteristic periodic acid-Schiff positive polyglucosan inclusions (Lafora bodies) (6-9). Substantial biochemical and histological studies of these bodies suggest LD is a generalized storage disease (8, 10, 11), but the presumed enzymatic defect regains unknown.
Linkage analysis and homozygosity mapping initially localized a Lafora's disease locus (EPM2A) to a region at chromosome 6q23-q25 bounded by the genetic markers D6S1003 and D6S311 (12, 13). However, there is a need in the art to more clearly define the region(s) mutated in Lafora's disease to allow for the development of accurate diagnostic assays for Lafora's disease. More specifically, there is a need to sequence the gene associated with Lafora's Disease and to identify mutations and/or deletions in the gene that are causative of Lafora's Disease.